Most ophthalmic drugs are delivered by topical application or direct injection into the vitreous, and many are limited by difficulties in sustaining therapeutic drug levels or by problems with patient adherence.
As effective as topical drops are for delivering medication to the eye, they are wholly dependent on patient adherence. Even patients with potentially blinding conditions like glaucoma can be startlingly noncompliant about drop-taking.
For patients with wet age-related macular degeneration (AMD), anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to stall progression and improve vision, yet questions remain regarding optimal administration. Are indefinite anti-VEGF injections sustainable or effective over the long term?
Given these challenges and questions, a number of sustained-release ophthalmic drugs are in development. The approaches that are being studied for sustained-release delivery of glaucoma medication cover a wide range of products, including punctal plugs, ocular surface inserts, drug-eluting contact lens microparticles, and intraocular depot implants. Some may be able to deliver medication for weeks, months, or even years. Here’s a look at where three companies stand with their plans to develop such drug delivery platforms.
Selkie Therapeutics. Founded by Morgan V. Fedorchak, PhD, assistant professor of ophthalmology at the University of Pittsburgh School of Medicine, Selkie Therapeutics has created a platform called the SoliDrop that combines a thermoresponsive hydrogel carrier with drug-loaded polymer microspheres. “The gel is administered just like a traditional liquid eyedrop and collects beneath the lower eyelid, where it forms a stable, non-degradable gel due to the increased temperature,” Dr. Fedorchak explains.
The polymer microspheres are designed to degrade slowly and predictably over one month for continuous release of drug concentration at levels much lower than traditional eyedrops yet high enough to be clinically effective.
“The SoliDrop reduces dosing frequency from multiple times per day down to once a month, which we believe – and the literature would suggest – will greatly improve patient adherence,” Fedorchak says. “By using a localized delivery depot and continuous drug release, we hit the target drug concentration and stay there for long time periods, which may make the system more effective,” he says.
Selkie has finished preclinical efficacy testing of the SoliDrop and is well into the remainder of its Investigational New Drug-enabling studies. In addition, the company is expanding to meet the demands of the technology and discussing potential partnerships. “We offer the ability to give these favorable release characteristics – safety and therapeutic efficacy – to any number of drugs, even those in development,” says Dr. Fedorchak.
Ocular Therapeutix. The punctal plug delivery system is the most studied because of its prior use in dry eye treatment. One sustained-release platform that has generated buzz is the sustained-release travoprost intracanalicular depot known as OTX-TP from Bedford, MA-based Ocular Therapeutix.
The device is composed of polyethylene glycol hydrogel and drug-containing microparticles and is visible under blue light with fluorescence, making it easy for the clinician to know if it has dislodged. In Phase II clinical trials, sustained-release travoprost produced clinically meaningful reduction of intraocular pressure for up to three months. Two Phase III trials have been planned, the first of which is to begin in the second half of this year.
Neurotech. For treatment of wet AMD, Neurotech Pharmaceuticals of Cumberland, RI, has developed an implantable, sustained drug-delivery system for local, long-term delivery of anti-VEGF medication. Currently in Phase II clinical trials, the platform, known as NT-503 ECT, could conceivably enter the market within the next several years, according to CEO Quinton Oswald.
NT-503 ECT can be thought of as an implantable “biofactory” with three components: a protein product, a cell line that synthesizes the protein, and a surrounding semipermeable membrane that permits both elution of the protein out of the device and entry of oxygen and nutrients into the device while protecting the cell line from immune recognition. Neurotech plans to report top‐line data from the Phase II program in the first half of 2017.
OIS Article Contributed by Michael Smolinsky, Chief Content Officer, Ethis Communications